Thermoregulation in neonates

and infants

Mark Ryan, MD, MSPH

Pediatric Surgery Critical Care Fellow

3/25/15

Importance of normothermia

• Silverman et al. 1958

▫ Poor temperature control correlated with increased neonatal morbidity and mortality

• If admission temperature <35o C

▫ EGA 23 weeks = 58% mortality

▫ EGA 24 weeks = 43% mortality

▫ EGA 25 weeks = 30% mortality

Newborns are prone to heat loss

• Increased ratio of surface area to body mass

▫ Term infants: 3x adult ratio

▫ Preterm/SGA: 4x adult ratio

• Thin skin with little subcutaneous fat

• Superficial blood vessels

Physiology of thermoregulation

Fetal Heat Production

• Thermogenesis suppressed in utero

▫ Intrauterine inhibition

• Most heat production from chemical reactions relating to growth/function

▫ Last trimester: 3-4 W/kg heat generated (2x adult)

Fetal temp 0.5o greater than mother

Fetal Heat Production

• Mechanisms of heat dissipation

▫ 15%: Conduction through skin into amniotic fluid

▫ 85%: Convectionthrough venous blood in placenta

Perinatal thermoregulation

• Governed by preoptic chiasma/anterior hypothalamic nuclei (POAH)▫ Receives central sensory input and info from

cutaneous temperature receptors

• Nonshivering thermogenesis▫ Activated by sympathetic NE secreting nerve

fibers▫ Innervate brown adipose tissue (BAT)

• Shivering thermogenesis ▫ Activated by posterior hypothalamic nucleus

Cold Sensation (Internal)

• Thermosensors in POAH

▫ Cooling evokes heat production and vasoconstriction

• Receptors also found in lower brainstem

▫ Midbrain and medulla oblongata

▫ Less sensitive than POAH

• Spinal cord

▫ Extremely sensitive

▫ Change of > 0.02o C sufficient to elicit shivering

Cold sensation (External)

• Fine unmyelinated nerve endings in basal layer of epidermis

• Have mitochondria connected to temp-sensitive Na/K pump

▫ Converts cold stimulus to electrical signal

▫ Exaggerated response to sudden change in temp

• Travel within spinothalamic tract in anterolateral spinal cord

• Change of 0.01o C sufficient to evoke sensation

Shivering

• Small, random muscle contractions

• Hydrolyzes ATP, + respiration, dissipates free energy as heat

• Primary motor center in posterior hypothalamus

▫ When hyper/euthermic, inhibited by POAH

• In adults, increases heat production 4-5x

Shivering

• 2nd line of defense for infant

▫ Higher surface to mass ratio

▫ Poorer thermal insulation

▫ Increases convective heat loss because of body oscillations

• Shivering ability not absent in neonates

▫ Observed with severe hypothermia

▫ Threshold is displaced to lower body temp

Nonshivering thermogenesis

• Brown adipose tissue (BAT)

▫ 0.5-1.5% of total infant body weight in 3rd TM, 2-7% at term

▫ Begins differentiation at 26-30 weeks

Continues development until 5 weeks after delivery

▫ Near highly perfused organs or adjacent to vessels

Predominantly near kidneys and intrascapular area of back extending up dorsal neck

▫ O2 consumption increased 10x on exposure to NE

Effect mediated by β3 and α1 receptors

Nonshivering thermogenesis

• Thermogenic properties due to action of uncoupling protein (UCP1)

▫ Found only in BAT

▫ Allows protons into mitochondrial matrix

▫ Uncouples oxidative phosphorylation from the production of ATP

• Preterm infants have lower amounts of BAT and decreased UCP1 expression

Mechanisms to control heat loss

• Vasomotor

▫ Noradrenergic sympathetic stimulation causes:

Vasoconstriction in acral areas (fingers, hands, ears, lips, nose)

Vasodilation in trunk and proximal limbs

Minimal vasoconstriction on head and brow

Mechanisms to control heat loss

• Behavioral Regulation

▫ Postural reactions against overheating

▫ Flexion of extremities

Decreases surface area available for heat loss

▫ Cry to signal thermal discomfort and alert caregiver

Effect of hypothermia on metabolic

rate • MR increases initially with decrease in body

temperature

▫ Can be prevented with deep general anesthesia

• Van’t Hoff’s law – rate of chemical reactions ⇧ 2-3x for every 10o C ⇧ in temperature

Effect of hypoxia on thermogenesis

• In animal studies, exposure to cold increases O2

consumption by 100% or more

• Increase is attenuated if hypoxic▫ Conserves oxygen that

would be used to generate heat

▫ May reduce or override sympathetic activation of BAT in response to cold

Effect of hypoxia on thermogenesis

• Anaerobic metabolism insufficient to produce enough heat for thermoregulation

• Shivering thermogenesis not affected

• Infants with chronic hypoxia (CHD) are still able to manifest thermogenic response

Response to heat

• Term newborns able to sweat at birth

▫ Greater density of sweat glands than adult

▫ Primarily on forehead, temple, occiput

• Sweating absent in infants <36 weeks EGA

▫ Appears by 2 weeks of age

• Vasodilation occurs in term and preterm infants

▫ Skin warm/red when overheated

• Will decrease activity, sleep more, lie in extended position

Fever

• Neonates are capable of temperature elevations above 38-39o C with septicemia, prurulentmeningitis, and pneumonia

• Nonshivering thermogenesis is prevailing response

Fever

• Set-point displacement

▫ Organism attempts to set and sustain a higher body temperature

• Activation of normal cold defense reactions at an elevated temperature

▫ Begins with peripheral vasoconstriction, central vasodilation

▫ Followed by enhanced thermogenesis

Adult = shivering

Infant = nonshivering thermogenesis

Fever

• Triggered by exogenous pyrogen (LPS)

▫ Stimulates granulocytes and macrophages to produce endogenous pyrogen (IL-1)

▫ IL-1 activates PLA2

Cell membrane phospholipids arachidonic acid

converted to PG

• PGE2 produces set point shift in hypothalamus

• Antipyretics (ASA) inhibit COX activity and PG formation

Environmental factors affecting

temperature

Mechanisms of heat loss

• Conduction▫ Transfer of heat from warm to

cool surface ▫ Objects in direct contact▫ 3% of body heat loss▫ Increased with wet clothing or

immersion

• Convection▫ Heat loss by air or fluid

circulating around the skin▫ 12-15% of body heat loss

Mechanisms of heat loss

• Radiation

▫ Infrared heat emission into surrounding air

▫ Primarily from head and non-insulinated areas

▫ 55-65% of heat loss

▫ Heat loss is proportional to temperature difference between adjacent surfaces

Independent of speed and temperature of intervening air

Mechanisms of heat loss

• Evaporation

▫ 560 calories of heat lost/mL evaporated water

▫ 25% of heat loss

¼ respiratory, ¾ transepidermal water loss (TEWL)

▫ Affects term infants at delivery (amniotic fluid)

▫ Preterm infants have increased TEWL

Thin, poorly keratinized stratum corneum

TEWL approaches that of newborn by 2-3 weeks

▫ Use of radiant warmer increases TEWL 0.5-2x

Measures to prevent heat loss

• Conduction

▫ Pre-warm objects coming to contact with infant

Bed, stethoscope, blankets

▫ Chemical thermal mattresses can be placed under preterm infants for rewarming

Measures to prevent heat loss

• Convection

▫ Cover with plastic prior to transport

▫ Keep sides of radiant warmer up/port holes in incubator closed

▫ Heat/humidify O2

▫ Minimize skin exposure to environment

Measures to prevent heat loss

• Evaporation

▫ No bathing if infant hypothermic or unstable

▫ Dry infant thoroughly after delivery

▫ Increase ambient humidity

▫ Plastic blanket/film – decreases H20 loss 75%

▫ Aquaphor/vegetable oil

Increased risk of coag negative staph infection

Measures to prevent heat loss

• Radiation

▫ Keep bed/incubator away from windows and outside walls

• Overheating can occur with radiant warmer or direct sunlight

Perioperative hypothermia

• Normal OR maintained at 23o C or below

• Multiple cold surfaces increase radiant heat loss

• Temperature gradient increases convective and evaporative heat loss

• Induction of anesthesia induces core to peripheral heat distribution

• Increased complications in infants

▫ Apnea, hypoxemia, hypercarbia, acidosis, impaired oxygen delivery

Perioperative Hypothermia

• 108 NICU patients who underwent surgical procedures in OR vs NICU▫ OR group had increased perioperative hypothermia

(65% vs 13%)▫ Hypothermic patients

3x higher rate of respiratory support interventions 6x higher rate of cardiac support interventions

• Hypothermia in adults results in increased wound infections, EBL, adverse cardiac events▫ Vasoconstriction decreases oxygen delivery to wound▫ Starvation and anesthesia blunt response to cold stress▫ Increased evaporative losses by exposed organs

Effect of hypothermia on metabolic

rate with anesthesia

Compensation lost at 30o C

Light anesthesia

Moderate anesthesia

Deep anesthesia

Management of the operating room

• OR temperature 28-30o C (82-86o F)

• Use of forced air warming systems or radiant heater

• Insulate infant during transport

• Minimize area of exposure

Therapeutic hypothermia

Hypoxic ischemic encephalopathy

• Intrapartum asphyxia resulting in diminished supply of oxygen and blood to the brain, resulting in neuronal injury

• Incidence 1-8/1000 live births worldwide

▫ Higher in areas without access to obstetric/perinatal care

• Extent of injury does not follow a wholly reproducible pattern

Hypoxic ischemic encephalopathy

• Precipitating conditions:▫ Prolapsed umbilical cord▫ Uterine rupture▫ Placental abruption▫ Amniotic fluid embolism▫ Acute maternal hemorrhage▫ Any condition with ⇩ maternal cardiac output and

fetal blood flow (anaphylaxis)▫ Acute neonatal hemorrhage

Vasa previa, bleeding from cord, fetal-maternal hemorrhage

Classification

• Stage 1 (mild)▫ Transient irritability, hypertonia, poor feeding▫ ~100% normal functional outcome

• Stage 2 (moderate)▫ Lethargy, hypotonia, hyporeflexia, seizure▫ 30-40% normal, 30-50% epilepsy

• Stage 3 (severe)▫ Profound stupor, coma, isoelectric EEG, flaccid,

decerebrate posturing▫ 50-75% mortality, 80-100% disability

Hypoxic ischemic encephalopathy

• Acute phase: 0-6 hrs

▫ Insufficiency delivery of O2 and substrates (glucose and lactate)

▫ Neurons and glia unable to maintain homeostasis

▫ ATP exhausted Na/K pump fails cell depolarizes

▫ Cl and H2O enter cell cytotoxic edema lysis

Hypoxic ischemic encephalopathy

• Reperfusion

▫ Oxidative metabolism recovers in 30-60 min

▫ Resolution of acute cell swelling

▫ Burst of superoxide and NO formation

▫ Breakdown of blood-brain barrier

Increased brain swelling

Degradation of basement membrane by MMPs

Hypoxic ischemic encephalopathy

• Latent phase (6-15 hrs)

▫ Activation of cell death pathways activated by:

Calcium influx – depolarization of mitochondria

Abnormal exitatory receptor signalling - ⇧ Ca influx

Loss of trophic support from astrocytic growth factors

Cytokine release

Activation of cell surface death receptors (Fas)

Effect of Cooling

• Suppression of programmed cell death

• Depression of metabolic activity

▫ Reduced oxygen demand

• Inhibits induction of proinflammatory cytokines

▫ IL-10, TNF α, IFN γ

• Reduced cytotoxic edema

• Reduced secondary injury (seizures)

Inclusion criteria:

• <6 hours since birth

• >36 weeks gestation

• >1800 grams

• Cord or neonatal blood gas pH <7.0 or BD >16

• Abnormal neurologic exam

▫ APGAR <3 after 5 minutes

• Experimental

▫ >6 hours since birth

▫ 34-36 weeks

Results

• 8 RCTs – 630 infants with moderate/severe HIE

▫ Decreased risk of major death/disability (RR 0.75)

Death RR 0.74, Disability RR 0.92

▫ Benefits seen with whole body cooling (vs. head)

▫ Adverse effects

Decreased baseline HR (RR 5.96)

Increased need for BP support (RR 1.17)

Platelet count <150 (RR 1.55)

No difference in arrhythmia, transfusion, bleeding, hypoglycemia, sepsis

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occurrence and impact on infant outcomes. Advances in neonatal care : official journal of the National Association of Neonatal Nurses 2014;14:154-64.

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Questions?